Expression of ectonucleotidase CD39 by Foxp3+ Treg cells:: hydrolysis of extracellular ATP and immune suppression
Expression of ectonucleotidase CD39 by Foxp3+ Treg cells:: hydrolysis of extracellular ATP and immune suppression
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DOI：
10.1182/blood-2006-12-064527
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发表时间：
2007-08-15
期刊：
影响因子：
20.3
通讯作者：
Falk, Kirsten
中科院分区：
文献类型：
--
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
在免疫系统中，细胞外ATP作为“天然佐剂”发挥作用，表现出多种促炎作用。它由受损细胞释放，作为创伤和细胞死亡的指标，但可以被CD 39（三磷酸核苷二磷酸水解酶-1 [NTPDase 1]）灭活，这是一种将ATP降解为AMP的胞外酶。在这里，我们发现CD 39主要由免疫抑制性Foxp 3（+）调节性T（Treg）细胞表达。在小鼠中，这种酶几乎存在于所有的CD 4（+）CD 25（+）细胞上。CD 39表达由Treg特异性转录因子Foxp 3驱动，其催化活性通过T细胞受体（TCR）连接而强烈增强。因此，活化的Treg细胞能够消除ATP相关作用，例如P2受体介导的细胞毒性和ATP驱动的树突细胞成熟。此外，人Treg细胞表达⑶ 39。与小鼠相反，人的CD 39表达仅限于Foxp 3+调节效应/记忆样T（T-REM）细胞的一个亚群。值得注意的是，缓解/复发型多发性硬化症（MS）患者血液中CD 39（+）Treg细胞的数量显著减少。因此，在人类中，CD 39是可能参与控制炎性自身免疫疾病的Treg亚群的标志物。
In the immune system, extracellular ATP functions as a "natural adjuvant" that exhibits multiple proinflammatory effects. It is released by damaged cells as an indicator of trauma and cell death but can be inactivated by CD39 (nucleoside triphosphate diphosphohydrolase-1 [NTPDase 1]), an ectoenzyme that degrades ATP to AMP. Here, we show that CD39 is expressed primarily by immune-suppressive Foxp3(+) regulatory T (Treg) cells. In mice, the enzyme is present on virtually all CD4(+)CD25(+) cells. CD39 expression is driven by the Treg-specific transcription factor Foxp3 and its catalytic activity is strongly enhanced by T-cell receptor (TCR) ligation. Activated Treg cells are therefore able to abrogate ATP-related effects such as P2 receptor-mediated cell toxicity and ATP-driven maturation of dendritic cells. Also, human Treg cells express CD39. In contrast to mice, CD39 expression in man is restricted to a subset of Foxp3+ regulatory effector/memory-like T (T-REM) cells. Notably, patients with the remitting/relapsing form of multiple sclerosis (MS) have strikingly reduced numbers of CD39(+) Treg cells in the blood. Thus, in humans CD39 is a marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease.